Generally, the usual method for preparation of globular, insoluble particles of a copolymer is by suspension copolymerization of a bifunctional monomer with a tetrafunctional cross-linking agent. The globular shape of the particles is necessary to achieve satisfactory efficiency when such copolymer particles are to be employed in chromatography.
Copolymerization of monomer with a small amount of cross-linking tetrafunctional comonomer results in the formation of gels which do not exhibit permanent porosity in a dry state and which swell in suitable solvents. The internal structures of such materials, as well as the degree of swelling at equilibrium thereof, are a function of the density of the cross-links, that is, the degree of cross-linking, in the copolymer and are dependent on the proportion of cross-linking monomer in the starting polymerization mixture. The gels prepared in this manner are generally homogeneous or microreticular and they are especially useful for the separation of low molecular weight compounds or oligomers having molecular weights up to about 4,000 by gel permeation chromatography. A lower density network, that is, less dense cross-linking can be achieved by decreasing the concentration of cross-linking monomer in the reaction mixture and the resulting gels are useful for separating compounds having higher molecular weight, that is, above about 4,000. On the other hand, as the concentration of the cross-linking monomer is decreased, the swollen particles of the copolymer tend to become insufficiently mechanically stable and became unsuitable as packing in chromatographic columns below a specific limit of concentration of cross-linking mononer which is dependent upon both its type and character of the monomer forming the main chain. At contents of cross-linking agent below 2% the mechanical stability is no more suited for high speed and high resolution gel chromatography. The cross-linking agents with higher affinity to the aqueous phase (diethyleneglycol dimethacrylate, methylene-bis-acrylamide etc.) require for reaching equal network density in swollen condition, a higher concentration of the cross-linking agent (about 5%). Generally, the microreticular gels so formed are not employed in gas chromatography.
The gels suitable for the separation of polymers are formed by copolymerization of a bifunctional monomer with a relatively large proportion of a cross-linking monomer, as mentioned hereinbefore, and usually in the presence of an inert component which in most cases is an organic solvent. However, the inert component may be either a solvent or precipitant of the copolymer. Due to the high concentration of the cross-linking monomer, the copolymer formed swells only very little and a separation of phases takes place during the course of the polymerization. The gels so prepared are heterogeneous. Moreover, when a precipitant for the copolymer is used as the inert component, the particles of the copolymer formed are permanently porous even in a dry state. Such permanently porous materials are macro-porous or macroreticular, have considerable surface area and are used in gas chromatography. The character and amount of the inert component, as well as the concentration of the cross-linking monomer in the starting monomer mixture, are the determining factors which control the copolymer heterogeneity.
The globular polymer particles formed must be fractionated according to size before using them in chromatographic applications. Therefore, it is desirable to carry out the suspension polymerization in a manner so that most of the globules formed lie in the required region and any distribution of particle sizes is kept as low or narrow as possible. Generally, in gel chromatography, the most convenient particle size is in a range of from about 40.mu. to about 80.mu. and in gas chromatography in a range of about 100.mu. to about 200.mu.. The presence of dust in the copolymer as well as the presence of particles of excessive size on non-globular shape detracts from the usefulness of the product.
Two factors or effects which negatively influence the copolymerization of hydrophilic monomer with hydrophobic comonomer in an aqueous dispersion medium are the solubility of water in the organic medium and the extraction of the hydrophilic monomer by or into the aqueous dispersion medium. When water dissolves in the monomer mixture or in the polymerizing particles, it can act as an undesirable inert component and substantially influence the structure of the resulting copolymer. On the other hand, where extraction of the hydrophilic monomer from the organic phase into the aqueous dispersion medium occurs, the ratio of both monomers in the polymerization mixture and in the polymerizing globules is changed in comparison to the initial ratio in the starting composition, and, accordingly, the network density of a homogeneous copolymer gel and the porosity of a macroporous copolymer-gel being formed are undesirably influenced. Moreover, in those cases where the hydrophilic monomer is extracted into the aqueous phase, it can also polymerize in solution and should the homopolymer so formed be insoluble in water and precipitate in the course of polymerization, it contributes to agglomeration of the suspension and complicates the subsequent fractionation. On the other hand, however, if the homopolymer formed dissolves in water, the viscosity of the dispersion medium increases during the course of the polymerization and the globular particles formed tend to have a more widely varied size distribution as they coagulate. In such cases, the stability of the suspension deteriorates substantially, the particles have an irregular shape and in the final stage the whole system collapses with the suspension precipitating partially or entirely.
These difficulties may be obviated by suppressing the solubility of the hydrophilic monomer in the aqueous phase by salting it out with a dispersion medium which is usually a concentrated solution of an inorganic salt and in which the finely dispersed water insoluble hydroxide, such as Mg (OH).sub.2 or salt is used as a suspension stabilizer. However, even when proceeding in this manner some partial dissolving of the hydrophilic monomer cannot be avoided as a rule. Furthermore, the copolymer thus obtained has to be treated to remove the suspension stabilizer therefrom. This treatment is relatively laborious and time consuming. Moreover, the problem of water solubility in monomer particles at the initiation of the polymerization is still not eliminated.
Suspension polymerization of a mixture of hydrophilic and hydrophobic monomers in a non-aqueous dispersion medium is another way in which particularly homogeneous gels having a low density of cross-links may be advantageously prepared. This method requires, however, the application of special suspension stabilizers to prevent extraction of the hydrophobic monomer into the suspension medium which is generally an organic solvent and most frequently oils and the like. Consequently, the oil phase has to be recovered after the reaction which makes the processing of the suspension relatively difficult and time consuming in this case also. Consequently, there exists a need for a method or process which does not exhibit the disadvantages of the methods discussed above. The present invention provides such a process.